Syndrome of inappropriate antidiuretic hormone (SIADH) is caused by excessive antidiuretic hormone (ADH) production despite low plasma osmolality or large plasma volume. It is characterised by euvolemic hyponatremia – dilutional hyponatremia with no evidence of extracellular fluid overload.
The diagnosis requires concentrated urine in the presence of hyponatremia and low plasma osmolality, in the absence of hypovolaemia, oedema, or diuretics.
- Causes (MADCHOP)
- Malignancy
- ADH secretion from an ectopic source
- Drugs such as SSRIs and ecstasy
- CNS disease – tumor, infection, Guillain-Barré Syndrome
- Hormone deficiency – hypothyroidism and adrenal insufficiency
- Other causes – porphyria, alcohol withdrawal
- Pulmonary causes – pneumonia, tuberculosis, lung abscess, sarcoidosis
- Signs and symptoms
- Nausea
- Myalgia
- General muscle weakness
- Hyporeflexia
- Ataxia
- Tremor
- Irritability
- Headache
- Cheyne-Stokes respiration
- Fits and coma if severe hyponatremia
- Investigations
- Euvolemic hyponatremia
- Plasma osmolality
- Urine sodium
- Urine osmolality
- High (concentrated urine)
- Normal renal, adrenal, and thyroid function
- Treatment
- Treat the underlying cause
- Mild or asymptomatic cases require no treatment
- Water restriction
- Demeclocycline if water restriction is ineffective or poorly tolerated
- Demeclocycline inhibits the action of ADH on the kidneys
- Vasoopressin receptor antagonists (tolvaptan) may be used
- Hypertonic saline + furosemide in severe cases
Biochemistry
| ACTH | P: <80 ng/L |
| ALT | P: 5–35 U/L |
| Albumin | P: 35–50 g/L |
| Aldosterone | P: 100–500 pmol/L |
| Alk. phosphatase | P: 30–130 U/L |
| α-Amylase | P: 0–180 IU/dL |
| α-Fetoprotein | S: <10 kU/L |
| Angiotensin II | P: 5–35 pmol/L |
| ADH | P: 0.9–4.6 pmol/L |
| AST | P: 5–35 U/L |
| Bicarbonate | P: 24–30 mmol/L |
| Bilirubin | P: 3–17 μmol/L |
| BNP | P: <50 ng/L |
| CRP | P: <10 mg/L |
| Calcitonin | P: <0.1 mcg/L |
| Calcium (ionized) | P: 1.0–1.25 mmol/L |
| Calcium (total) | P: 2.12–2.60 mmol/L |
| Chloride | P: 95–105 mmol/L |
| Cholesterol | P: <5.0 mmol/L |
| VLDL | P: 0.128–0.645 mmol/L |
| LDL | P: <2.0 mmol/L |
| HDL | P: 0.9–1.93 mmol/L |
| Cortisol AM | P: 450–700 nmol/L |
| Cortisol Midnight | P: 80–280 nmol/L |
| CK ♂ | P: 25–195 U/L |
| CK ♀ | P: 25–170 U/L |
| Creatinine | P: 70–100 μmol/L |
| Ferritin | P: 12–200 mcg/L |
| Folate | S: 2.1 mcg/L |
| FSH | P: 2–8 U/L ♂; >25 menopause |
| GGT ♂ | P: 11–51 U/L |
| GGT ♀ | P: 7–33 U/L |
| Glucose (fasting) | P: 3.5–5.5 mmol/L |
| Growth hormone | P: <20 mu/L |
| HbA1C (DCCT) | B: 4–6% |
| HbA1C (IFCC) | B: 20–42 mmol/mol |
| Iron ♂ | S: 14–31 μmol/L |
| Iron ♀ | S: 11–30 μmol/L |
| Lactate (venous) | P: 0.6–2.4 mmol/L |
| Lactate (arterial) | P: 0.6–1.8 mmol/L |
| LDH | P: 70–250 U/L |
| LH | P: 3–16 U/L |
| Magnesium | P: 0.75–1.05 mmol/L |
| Osmolality | P: 278–305 mosmol/kg |
| PTH | P: 0.8–8.5 pmol/L |
| Potassium | P: 3.5–5.3 mmol/L |
| Prolactin ♂ | P: <450 U/L |
| Prolactin ♀ | P: <600 U/L |
| PSA | P: 0–4 mcg/mL |
| Protein (total) | P: 60–80 g/L |
| Red cell folate | B: 0.36–1.44 μmol/L |
| Renin (erect) | P: 2.8–4.5 pmol/mL/h |
| Renin (recumbent) | P: 1.1–2.7 pmol/mL/h |
| Sodium | P: 135–145 mmol/L |
| TBG | P: 7–17 mg/L |
| TSH | P: 0.5–4.2 mU/L |
| T4 | P: 70–140 nmol/L |
| Free T4 | P: 9–22 pmol/L |
| TIBC | S: 54–75 μmol/L |
| Triglycerides | P: 0.50–2.3 mmol/L |
| T3 | P: 1.2–3.0 nmol/L |
| Troponin T | P: <0.1 mcg/L |
| Urate ♂ | P: 210–480 μmol/L |
| Urate ♀ | P: 150–390 μmol/L |
| Urea | P: 2.5–6.7 mmol/L |
| Vitamin B12 | S: 0.13–0.68 nmol/L |
| Vitamin D | S: 50 nmol/L |
Arterial Blood Gases
| pH | 7.35–7.45 |
| PaCO₂ | 4.7–6.0 kPa |
| PaO₂ | >10.6 kPa |
| Base excess | ±2 mmol/L |
Urine
| Cortisol (free) | <280 nmol/24h |
| Hydroxyindole acetic acid | 16–73 μmol/24h |
| Hydroxymethylmandelic acid | 16–48 μmol/24h |
| Metanephrines | 0.03–0.69 μmol/mmol cr. |
| Osmolality | 350–1000 mosmol/kg |
| 17-Oxogenic steroids ♂ | 28–30 μmol/24h |
| 17-Oxogenic steroids ♀ | 21–66 μmol/24h |
| 17-Oxosteroids ♂ | 17–76 μmol/24h |
| 17-Oxosteroids ♀ | 14–59 μmol/24h |
| Phosphate (inorganic) | 15–50 mmol/24h |
| Potassium | 14–120 mmol/24h |
| Protein | <150 mg/24h |
| Protein/creatinine ratio | <3 mg/mmol |
| Sodium | 100–250 mmol/24h |
Haematology
| WCC | 4.0–11.0 ×10⁹/L |
| RBC ♂ | 4.5–6.5 ×10¹²/L |
| RBC ♀ | 3.9–5.6 ×10¹²/L |
| Hb ♂ | 130–180 g/L |
| Hb ♀ | 115–160 g/L |
| PCV ♂ | 0.4–0.54 L/L |
| PCV ♀ | 0.37–0.47 L/L |
| MCV | 76–96 fL |
| MCH | 27–32 pg |
| MCHC | 300–360 g/L |
| RDW | 11.6–14.6% |
| Neutrophils | 2.0–7.5 ×10⁹/L (40–75%) |
| Lymphocytes | 1.0–4.5 ×10⁹/L (20–45%) |
| Eosinophils | 0.04–0.44 ×10⁹/L (1–6%) |
| Basophils | 0–0.10 ×10⁹/L (0–1%) |
| Monocytes | 0.2–0.8 ×10⁹/L (2–10%) |
| Platelets | 150–400 ×10⁹/L |
| Reticulocytes | 0.8–2.0% / 25–100 ×10⁹/L |
| Prothrombin time | 10–14 s |
| APTT | 35–45 s |
Paediatric
| Pulse Rate (bpm) |
|---|
| Neonate | 140–160 |
| Infant <1yr | 120–140 |
| 1–5 years | 110–130 |
| 5–12 years | 80–120 |
| >12 years | 70–100 |
| Respiratory Rate (tachypnoea) |
|---|
| 0–2 months | ≥60/min |
| 2–12 months | ≥50/min |
| 1–5 years | ≥40/min |
| >5 years | ≥30/min |
| Blood Pressure (mmHg) |
|---|
| Term | 65/45 |
| 1 year | 75/50 |
| 4 years | 85/60 |
| 8 years | 95/65 |
| 10 years | 100/70 |
| Weight Formulas |
|---|
| 3–12 months | (a + 9)/2 kg |
| 1–6 years | 2a + 8 kg |
| >6 years | (7a − 5)/2 kg |
| Haemoglobin (g/dL) |
|---|
| Term newborn | 13–20 |
| 1 month | 11–18 |
| 2 months | 10–15 |
| 1–2 years | 10–13 |
| >2 years | 11–14 |
| MUAC (6 months–5 years) |
|---|
| Obese | >17.5 cm |
| Normal | 13.5–17.4 cm |
| At risk | 12.5–13.4 cm |
| Moderate malnutrition | 11.5–12.4 cm |
| Severe malnutrition | <11.5 cm |
| Developmental Milestones |
|---|
| Social smile | 1.5 months |
| Head control | 4 months |
| Sits unsupported | 7 months |
| Crawls | 10 months |
| Stands unsupported | 10–12 months |
| Walks | 12–13 months |
| Talks | 18 months |
| CSF WBC (/mm³) |
|---|
| Term newborn | 0–25 |
| >2 weeks | 0–5 |
